Tetrahydrofuran → HCID 178482917, compound

HRID 1909041Notes

Reaction equation

HRID 1909041 reaction equation
BrC1C=C(C([C:10]2[N:14](COCC[Si](C)(C)C)[C:13]3[CH:23]=[CH:24][C:25]([N:27]4[CH2:32][CH2:31][CH:30]([N:33]([CH3:35])[CH3:34])[CH2:29][CH2:28]4)=C[C:12]=3[N:11]=2)=O)C=CN=1.C[O:37][C:38](=O)[C:39]1[CH:44]=[CH:43][C:42]([C:45]#[N:46])=[C:41]([C:47]2[C:56]3[C:51](=CC=C[CH:55]=3)[CH:50]=[N:49][CH:48]=2)[CH:40]=1.C([N-:61]C(C)C)(C)C.[Li+].O1C[CH2:69][CH2:68][CH2:67]1>>[CH3:35][N:33]([CH3:34])[CH:30]1[CH2:29][CH2:28][N:27]([C:25]2[N:61]=[C:12]3[NH:11][C:10]([C:38]([C:39]4[CH:44]=[CH:43][C:42]([C:45]#[N:46])=[C:41]([C:47]5[C:56]6[C:51](=[CH:67][CH:68]=[CH:69][CH:55]=6)[CH:50]=[N:49][CH:48]=5)[CH:40]=4)=[O:37])=[N:14][C:13]3=[CH:23][CH:24]=2)[CH2:32][CH2:31]1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 2724682Lithium diisopropylamideHCID 66599496Methyl 4-cyano-3-(4-isoquinolinyl)benzoateHCID 86664348(2-Bromo-pyridin-4-yl)-[5-(4-dimethylamino-piperidin-1-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yl]-methanone

Product 1

HCID 178482917HCID 178482917, compoundYield 3%

Conditions

Temperature
-78 °C

Procedure

The mixture of 5-(4-dimethylamino-piperidin-1-yl)-imidazo[4,5-b]pyridin-3-carboxylic acid tert-butyl ester (Example 1) (50 mg, 0.145 mmole), 4-cyano-3-isoquinolin-4-yl-benzoic acid methyl ester (41 mg, 0.145 mmole), and tetrahydrofuran (3 ml) was cooled to −78° C. Lithium diisopropylamide (2N, 0.15 ml, 0.30 mmole) was added slowly. Reaction mixture was stirred at −78° C. for 2 hours and then was quenched with water, extracted with EtOAc. EtOAc layer was concentrated and crude product was purified by using HPLC (20% to 100% acetonitrile/water with 0.1% NH4OH) to afford 4-[5-(4-dimethylamino-piperidin-1-yl)-3H-imidazo[4,5-b]pyridine-2-carbonyl]-2-isoquinolin-4-yl-benzonitrile (2 mg, 3%) as a yellow solid. 1H NMR (400 MHz, CD3OD) δ 1.59 (m, 2H), 1.98 (m, 2H), 2.31 (s, 6H), 2.44 (m, 2H), 3.14 (m, 1H), 3.02 (m, 2H), 4.50 (m, 2H), 6.86 (d, J=9.03 Hz, 1H), 7.00 (d, J=8.03 Hz, 1H), 7.78 (m, 2H), 7.89 (d, J=9.54 Hz, 1H), 8.08 (d, J=8.03 Hz, 1H), 8.18 (J=7.03 Hz, 1H), 8.62 (s, 1H), 8.81 (s, 1H), 8.86 (d, J=8.03 Hz, 1H), 9.43 (s, 1H). HR-MS m/z 502.2357 (M+1).

Workup

  1. customReaction mixture
  2. customwas quenched with water
  3. extractionextracted with EtOAc
  4. concentrationEtOAc layer was concentrated
  5. customcrude product was purified

Sources & evidence

ORD record
ord-e5cb561a6f74420197a51805fc7ff2bd
Source dataset
uspto-grants-2013_12
Patent number
US08598217B2

Reaction notes

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